Studies on the induction of immunologic unresponsiveness. I. Effects of endotoxin and phytochemagglutinin.

Summary The time course of the inhibition of establishment of immunologic unresponsiveness to human γ-globulin (HGG) in adult mice by endotoxin (ET) has been studied. ET prevents the establishment of unresponsiveness in C57BL/6J and A/J mice only if given up to 2 days after injection of HGG. ET given before or 3 or more days after HGG is ineffective. The effect of ET on induction of unresponsiveness is apparently independent of the granulopectic activity of the reticuloendothelial system (RES), as measured by clearance of colloidal carbon from the circulation, since ET is effective when the activity of the RES is either elevated or depressed. One dose of ET before HGG eliminates the ability of the ET given after HGG to prevent the establishment of immunologic unresponsiveness, although the granulopectic activity of the RES is elevated. The amount of HGG associated with spleen cells is comparably elevated above controls in animals treated with ET before or after HGG. The effect is not the result of complex formation between ET and HGG. Cortisone given at the time of ET does not alter the effect of ET. Phytohemagglutinin (PHA) induces an intense proliferation of spleen cells in vivo as measured by incorporation of tritiated thymidine and increase in cell number, but has no effect on the induction of immunologic unresponsiveness. Neither ET nor PHA affect the unresponsive state which has been induced in neonatal life.